obtaining-human-microglia-from-adult-human-brain-tissue

Obtaining Human Microglia from Adult Human Brain Tissue

Microglia are resident innate immune cells of the central nervous system (CNS). Microglia play a critical role during development, in maintaining ...

Indian Institute of Technology Jodhpur

Gliomas are the most prevalent primary brain tumors with immense clinical heterogeneity, poor prognosis and survival. The nucleotide-binding domain, and leucine-rich repeat containing receptors (NLRs) and absent-in-melanoma 2 (AIM2) are innate immune receptors crucial for initiation and progression of several cancers. There is a dearth of reports linking NLRs and AIM2 to glioma pathology. NLRs are expressed by cells of innate immunity, including monocytes, macrophages, dendritic cells, endothelial cells, and neutrophils, as well as cells of the adaptive immune system. NLRs are critical regulators of major inflammation, cell death, immune and cancer-associated pathways. We used a data-driven approach to identify NLRs, AIM2 and NLR-associated gene expression and methylation patterns in low grade glioma and glioblastoma, using The Cancer Genome Atlas (TCGA) patient datasets. Since TCGA data is obtained from tumor tissue, comprising of multiple cell populations including glioma cells, endothelial cells and tumor-associated microglia/macrophages we have used multiple cell lines and human brain tissues to identify cell-specific effects. TCGA data mining showed significant differential NLR regulation and strong correlation with survival in different grades of glioma. We report differential expression and methylation of NLRs in glioma, followed by NLRP12 identification as a candidate prognostic marker for glioma progression. We found that Nlrp12 deficient microglia show increased colony formation while Nlrp12 deficient glioma cells show decreased cellular proliferation. Immunohistochemistry of human glioma tissue shows increased NLRP12 expression. Interestingly, microglia show reduced migration towards Nlrp12 deficient glioma cells.

Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma.

Apoptosis associated speck like protein containing CARD (ASC) is widely researched and recognized as an adaptor protein participating in inflammasome assembly and pyroptosis. It contains a bipartite structure comprising of a pyrin and a caspase recruitment domain (CARD) domain. These two domains help ASC function as an adaptor molecule. ASC is encoded by the gene PYCARD. ASC plays pivotal role in various diseases as well as different homeostatic processes. ASC plays a regulatory role in different cancers showing differential regulation with respect to tissue and stage of disease. Besides cancer, ASC also plays a central role in sensing, regulation, and/or disease progression in bacterial infections, viral infections and in varied inflammatory diseases. ASC is expressed in different types of immune and non-immune cells. Its localization pattern also varies with different kinds of stimuli encountered by cell. This review will summarize the literature on the structure cellular and tissue expression, localization and disease association of ASC.

Article	Year
Differential Expression Profile of NLRs and AIM2 in Glioma and Implications for NLRP12 in Glioblastoma. Scientific reports\| PubMed ID: 31186453	2019
Comprehensive review of ASC structure and function in immune homeostasis and disease. Molecular biology reports\| PubMed ID: 32124174	2020

Ishan Agrawal

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